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Background Total lung capacity (TLC) has been estimated with use of chest radiographs based on time-consuming methods, such as planimetric techniques and manual measurements. Purpose To develop a deep learning-based, multidimensional model capable of estimating TLC from chest radiographs and demographic variables and validate its technical performance and clinical utility with use of multicenter retrospective data sets. Materials and Methods A deep learning model was pretrained with use of 50 000 consecutive chest CT scans performed between January 2015 and June 2017. The model was fine-tuned on 3523 pairs of posteroanterior chest radiographs and plethysmographic TLC measurements from consecutive patients who underwent pulmonary function testing on the same day. The model was tested with multicenter retrospective data sets from two tertiary care centers and one community hospital, including (a) an external test set 1 ( n = 207) and external test set 2 ( n = 216) for technical performance and (b) patients with idiopathic pulmonary fibrosis ( n = 217) for clinical utility. Technical performance was evaluated with use of various agreement measures, and clinical utility was assessed in terms of the prognostic value for overall survival with use of multivariable Cox regression. Results The mean absolute difference and within-subject SD between observed and estimated TLC were 0.69 L and 0.73 L, respectively, in the external test set 1 (161 men; median age, 70 years [IQR: 61-76 years]) and 0.52 L and 0.53 L in the external test set 2 (113 men; median age, 63 years [IQR: 51-70 years]). In patients with idiopathic pulmonary fibrosis (145 men; median age, 67 years [IQR: 61-73 years]), greater estimated TLC percentage was associated with lower mortality risk (adjusted hazard ratio, 0.97 per percent; 95% CI: 0.95, 0.98; P < .001). Conclusion A fully automatic, deep learning-based model estimated total lung capacity from chest radiographs, and the model predicted survival in idiopathic pulmonary fibrosis. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Sorkness in this issue.